Alterations in the Processing of Rat-Liver Ribosomal RNA Caused by Cycloheximide Inhibition of Protein Synthesis

Publisher Website
Google Scholar
Abstract
Cycloheximide given in vivo at low doses (2-5 mg/kg body wt) causes within 30 min a complete inhibition of protein synthesis in rat liver. The labeling of nuclear proteins is also stongly inhibited. Under these conditions, the amount of nucleolar 45-S pre-rRNA and its [14C]-orotate labeling remain unaffected for at least 4 h. Initially the rates of synthesis and processing of 45-S pre-rRNA are not appreciably altered. Drastic alterations in the 45-S pre-rRNA processing pathways occur at the early stages of cycloheximide action. Formation of 18-S rRNA is abolished and that of 28-S rRNA is reduced to about half the level in control rats. This dichotomy in the production of the 2 ribosomal particles may be correlated with a block in the formation of 41-S and 21-S pre-rRNA. Generation of 36-S and 32-S pre-rRNA is still taking place but the rate of their processing to nucleolar 28-S rRNA is decreased, causing the accumulation of these 2 pre-rRNA species. Processing of 45-S pre-rRNA to an aberrant 39-S rRNA species is markedly enhanced. The channelling of nucleolar pre-rRNA along alternative processing pathways is apparently under stringent control by the continuous supply of critical protein(s).